FDA Grants Accelerated Approval for a New Alzheimer’s Disease Treatment

On January 6, 2023, the U.S. Food and Drug Administration used the “Accelerated Approval” process to approve a drug, Leqembi, for the treatment of Alzheimer’s disease.  Leqembi “is the second of a new category of medications approved for Alzheimer’s disease that target the fundamental pathophysiology of the disease.”

According to the director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, (CDER), the drug targets the “underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.” Currently, Alzheimer’s (a progressive brain disorder) affects over 6.5 million Americans and the families of the people who care for the people with the disease. Alzheimer’s destroys a person’s memory and ability to think. In time, the patient has difficulty performing even simple tasks.

The specific causes of the disease are not completely known. The main characteristic is known. Brain changes, “including amyloid beta plaques and neurofibrillary, or tau, tangles” cause a loss of neurons and their connections. These changes affect the ability of someone with Alzheimer’s to think and remember.

What is Alzheimer’s?

According to the FDA, Alzheimer’s disease causes brain cells to stop functioning, lose connections with other brain cells, and die over the course of many years. Why people develop Alzheimer’s is not known. What is known that is the disease tends to get progressively worse. The disease mainly affects people who are older than 60. Generally, African American and Hispanic/Latinos have a higher risk of developing Alzheimer’s disease than older white adults.

Other risk factors include being female; a prior moderate or severe head injury; a family history of the disease, having heart disease, stroke, high blood pressure, diabetes, or obesity; and lack of engagement in physical, social, and mental activities.

There is no cure for the disease. Current treatments include a few FDA-approved drugs that help patients keep their mental function and slow down or delay the symptoms. The current treatments also include managing behavioral symptoms such as anxiety and high blood pressure.

What is the FDA’s accelerated approval program?

The FDA began the “Accelerated Approval Program” so that some drugs that treat serious health disorders can fill an “unmet medical need based on a surrogate endpoint.” 

A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.”

Normally, according to the FDA, determining whether a drug does provide a benefit (the patient feels better, functions better, or lives) can take years. A clinical benefit is a “positive therapeutic benefit.” In 2012, Congress passed the Food and Drug Administration Safety Innovations Act (FDASIA) authorized the accelerated approval of a drug.

As an example of the benefit of using a surrogate/intermediate endpoint, the FDA could approve a drug that extends the life of a cancer patient, “based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit.” The maker of the cancer drug will still need to conduct studies “to confirm that tumor shrinkage actually predicts that patients will live longer.”

As with the hypothetical cancer drug, drug makers must still conduct studies to verify the anticipated clinical benefit does exist. Approval of a medication approved through the accelerated approval process can be withdrawn or the “labeled indication of the drug changed” if the study does not confirm the clinical benefit.

Approval of the Alzheimer’s drug Leqembi

In addition to the FDA approval of Leqembi, the FDA reports that the results of a “Phase 3 randomized, controlled clinical trial” to confirm the drug’s clinical benefit should be available soon.

The efficacy of Leqembi was already examined in 856 patients with Alzheimer’s disease in a “double-blind, placebo-controlled, parallel-group, dose-finding study.” The drug treatment began by evaluating patients with mild stages of the disease and a “confirmed presence of amyloid beta pathology.”  The study found that the patients who received the drug “had significant dose- and time-dependent reduction of amyloid beta plaque.” The patients who received the drug were given an “approved dose of lecanemab, 10 milligram/kilogram every two weeks.” The patients were found to have “a statistically significant reduction in brain amyloid plaque from baseline to Week 79” compared to the patients who received a placebo and had no amyloid beta plaque reduction.

The existence of:

“amyloid beta plaque was quantified using positron emission tomography (PET) imaging to estimate the brain levels of amyloid beta plaque in a composite of brain regions expected to be widely affected by Alzheimer’s disease pathology compared to a brain region expected to be spared of such pathology.”

The prescribing information for Leqembi includes:

• Warnings about amyloid-related imaging abnormalities (ARIA) including the risk of temporary brain swelling and a risk of infusion-related reactions which cause flu-like symptoms and other health problems.
• Warnings that “Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”
• Warnings that “there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.”

How does the FDA approve drugs without the accelerated approval process?

The FDA states that generally drug manufacturers must obtain approval to sell drugs in the US by testing the drug:

• The drug company or a sponsor should perform laboratory and animal tests to discover how the drug works and whether the drug is expected to be safe and work in humans.
• Next, a series of tests on humans are started to verify that the drug is safe when used to treat a disease and that the drug provides actual health benefits.
• The drug company then sends the data from these tests to the FDA’s Center for Drug Evaluation and Research (CDER).
• “A team of CDER physicians, statisticians, chemists, pharmacologists, and other scientists reviews the company’s data and proposed labeling.” The drug should be approved for sale if the CDER analysis confirms that the health benefits of the drug exceed the known drugs.

The FDA also regulates “over-the-counter (OTC) drugs” through OTC Drug monographs. “OTC drug monographs are a kind of ‘recipe book’ covering acceptable ingredients, doses, formulations, and labeling.” Monographs are routinely updated with new ingredients and labels. If a proposed product conforms to a monograph, no further FDA approval is needed to approve the drug. Otherwise, the drug will need to be reviewed separately and approved through the “New Drug Approval System.”

Most drugs are approved either based on their similarity to already approved drugs (the monograph method) or through a new drug analysis. To help people with serious health problems, the FDA also uses the accelerated approval process that provides approval based on an intermediary analysis of the drug’s health benefits provided a subsequent study is done to confirm the efficacy of the drug. The FDA recently approved the drug Leqembi for the treatment of Alzheimer’s disease through the accelerated approval process.

Drug companies and physicians should contact Cohen Healthcare Law Group, PC to review how drugs are approved by the FDA and what drugs have been approved by the FDA. Our experienced healthcare attorneys advise drug manufacturers and medical practices about healthcare compliance laws and regulations.